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Journal of Virology, August 2008, p. 7988-7999, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00894-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Novel Cellular Protein, VPEF, Facilitates Vaccinia Virus Penetration into HeLa Cells through Fluid Phase Endocytosis{triangledown} ,{dagger}

Cheng-Yen Huang, Tsai-Yi Lu, Chi-Horng Bair,{ddagger} Yuan-Shau Chang,§ Jeng-Kuan Jwo, and Wen Chang*

Institute of Molecular Biology, Academia Sinica, 128, Sec. 2, Academia Rd., Nankang, Taipei 11529, Taiwan, Republic of China

Received 28 April 2008/ Accepted 2 June 2008

Vaccinia virus is a large DNA virus that infects many cell cultures in vitro and animal species in vivo. Although it has been used widely as a vaccine, its cell entry pathway remains unclear. In this study, we showed that vaccinia virus intracellular mature virions bound to the filopodia of HeLa cells and moved toward the cell body and entered the cell through an endocytic route that required a dynamin-mediated pathway but not a clathrin- or caveola-mediated pathway. Moreover, virus penetration required a novel cellular protein, vaccinia virus penetration factor (VPEF). VPEF was detected on cell surface lipid rafts and on vesicle-like structures in the cytoplasm. Both vaccinia virus and dextran transiently colocalized with VPEF, and, importantly, knockdown of VPEF expression blocked vaccinia virus penetration as well as intracellular transport of dextran, suggesting that VPEF mediates vaccinia virus entry through a fluid uptake endocytosis process in HeLa cells. Intracellular VPEF-containing vesicles did not colocalize with Rab5a or caveolin but partially colocalized with Rab11, supporting the idea that VPEF plays a role in vesicle trafficking and recycling in HeLa cells. In summary, this study characterized the mechanism by which vaccinia virus enters HeLa cells and identified a cellular factor, VPEF, that is exploited by vaccinia virus for cell entry through fluid phase endocytosis.

* Corresponding author. Mailing address: Institute of Molecular Biology, Academia Sinica, 128, Sec. 2, Academia Rd., Nankang, Taipei 11529, Taiwan, Republic of China. Phone: 886-2-2789-9230. Fax: 886-2-2782-6085. E-mail: mbwen{at}ccvax.sinica.edu.tw

{triangledown} Published ahead of print on 11 June 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Hsinchu Science Park, Jhunan, Miaoli County, Taiwan, Republic of China.

§ Deceased.

Journal of Virology, August 2008, p. 7988-7999, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00894-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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